Table 1 Anti-DILI effect and mechanism of flavonoids in natural medicines
From: Mechanism of drug-induced liver injury and hepatoprotective effects of natural drugs
No. | Natural medicine | Bioactive components | Mechanisms | The species investigated | References |
|---|---|---|---|---|---|
1 | Fructus Livistonae | Total flavonoids | Decreased the level of AST and MDA, increase the level of GSH and SOD, and inhibit the expressions of iNOS protein and NT protein | Pre-clinical model: L02 cell | [65] |
2 | Polygonum perfoliatum L | Total flavonoids | Inhibition the Fas pathway and anti-inflammatory; Nrf2—ARE signal pathway | Pre-clinical model: Male SPF mice (6–8 weeks old, 18–22 g); Kunming mice (30 males and 30 females) weighing,18–22 g | |
3 | Toona sinensis (Juss.) M.Roem | Quercitrin | Inhibition of pro-inflammatory genes via the suppressions of JNK and p38 signaling Protects the mitochondria and anti-oxidative stress | Pre-clinical model: 30 male Balb/c mice (6 weeks old, 20-25 g); Male BALB/c mice (18–22 g) | |
4 | Polygonum orientale L | Isoorientin | Activating Nrf2 via the AMPK/Akt/GSK3β pathway | Pre-clinical model: Wild-type and Nrf2-/-(knockout) C57BL/6 mice | [70] |
5 | Sedum sarmentosum Bung | Total flavonoids, Isorhamnetin | Decrease the content of MDA, increase the content of GSH, increase the activity of SOD and GSH-Px activity, and lower the release of ALT and AST | Pre-clinical model: L02 cell | [71] |
6 | Pelargonium hortorum | Pelargonidin | Removing excessive ROS, reduce levels of necrosis, inflammation, and hepatocyte apoptosis | Pre-clinical model: Male C57BL/6 mice (8Â weeks old) | [72] |
7 | Scutellaria baicalensis Georgi | Baicalin, Baicalein | ERK Signaling Pathway, anti-inflammatory, ERK1/2 and PKC, | Pre-clinical model: Adult male C57BL/6 (B6) mice (8–10 weeks old); SPS male C57BL/6 mice (16–20 g) | |
8 | Glycyrrhiza uralensis Fisch | Glycyrrhizic acid | Down-regulation of CYP2E1 expression and deactivation of HMGB1-TLR4 signal pathway | Male Balb/c mice(8–10 weeks old) | [75] |
9 | Rosa laevigata Michx | Total flavonoids | Increase the protein expressions of Procaspase-3, Procaspase-8, FasL, Prohibitin and Bcl-2, and markedly decrease the protein expressions of Fas, Bax, p53 and NF-κB p65 | Pre-clinical model: Male Kunming mice, (18–22 g) | [76] |
10 | Penthorum chinense Pursh | Pinocembrin | Reduce the level of MDA and significant increases in SOD activity and GSH level. Inhibition of liver oxidative stress | Pre-clinical model: 50 male C57BL/6Â J mice | [77] |
11 | Silybum marianum (L.) Gaertn | Silymarin | Lower GSSG content, lower HO-1 induction, alleviated nitrosative stress, decreased p-JNK activation. improve ALT, AST, BUN, SCr and tissue NO levels | Pre-clinical model: Male BALB/c mice; Female mice (8–10 weeks, 30–35 g); Male Wistar rats (150–180 g) | |
12 | Hypericum monogynum L | Hyperoside | Inhibition of the formation of toxic intermediates and promotes APAP liver detoxification | Pre-clinical model: Male Kunming mice (6 weeks old, 20–25 g) | [81] |
13 | Garcinia mangostana | α-otwistinin | Inhibiting oxidative stress and attenuates inflammatory response through NF-κB and MAPK signaling pathways | Pre-clinical model: Male ICR mice (4–5 weeks old, 20–25 g) | [82] |
14 | Glycyrrhiza uralensis Fisch | Licochalcone A | Protective effect of Nrf2-mediated oxidative stress on APAP-induced liver injury | Pre-clinical model: Nrf2 −/− (knockout) C57BL/6 mice | [83] |
15 | Kaempferol galanga L | Kaempferol | Antioxidative stress, promoting metabolism and inhibiting inflammation | Pre-clinical model: L02 cell | [84] |
16 | Glycyrrhiza uralensis Fisch | Monoammonium glycyrrhizin | Regulation of expression of hepatobiliary membrane transporters | Pre-clinical model: Male Wistar rats (180–220 g) | [85] |
17 | Bacopa monnieri (L.) Wettst | Bacoside | Enhance liver antioxidant capacity and reduce oxidative stress | Pre-clinical model: Female Wistar albino rats (170–200 g) | [86] |
19 | Crataegus pin.nati fida Bge Curcuma longa L | Quercetin and Curcumin | Mitigated the rise in TBARS and restored the activities of antioxidant enzymes. Protected liver histology, normalized liver and kidney functions | Pre-clinical model: Male Wistar rats (64, 200–235 g) | [87] |
20 | Glycyrrhiza uralensis Fisch | Glycyrrhizic acid | Inhibition of hepatocyte apoptosis induced by TNF-α | Pre-clinical model: Male C57BL/6 wild-type mice (6–8 weeks old) | [88] |